Submitted in response to RFA AA-99-003, this application requests five years' support to study consequences and mechanisms of adolescent alcohol abuse in adult and adolescent twin pairs. The research proposal builds on two ongoing twin-family studies conducted in Finland. One study, FinnTwin16, has ascertained 2,800 twin pairs, born 1975-79, and assessed them, and their parents, with questionnaires, in 1991-1995, as the twins reached age 16; follow-up questionnaire assessments of the twins were made at ages 17 and 18 1/2. We propose a fourth questionnaire assessment of all these Finnish twins, at ages 22-25, to evaluate their adult use/abuse of alcohol and their social, educational, occupational and interpersonal competencies. From the adolescent questionnaire assessments, we have identified >200 dizygotic twin pairs for intensive follow-up; the targeted co- twins were selected for extreme concordance or extreme discordance for adolescent alcohol abuse. At ages 22-25, we will interview them with the Semi-Structured Assessment for Genetics of Alcoholism (SSAGA), access them with a neuropsychological test battery and evaluate their electrophysiological function with ERP paradigms. These within-family comparisons of co-twins discordant for adolescent alcohol abuse will robustly test for its consequences. To compliment this appraisal of early adult consequences of adolescent problem drinking, we propose intensive study of two birth cohorts from a second on-going study, FinnTwin12; 485 twin pairs, born 1986-87, are selected for intensive study in that project with 50% at elevated familial risk for alcoholism. At age 14, in years 2000-01, these twin pairs will be interviewed with the adolescent SSAGA (with other funding), and as part of this proposal, we will append to the interview an enriched neuropsychological test battery and assay testosterone and cortisol from saliva. Jointly, these neurophysiological, neuropsychological, and neuroendocrine studies of targeted Finnish twins, for whom risk-relevant data have been collected earlier, will offer incisive analyses of neurobiological mechanisms and consequences of alcohol abuse in adolescence.